TPCA-1 #50902

TPCA-1 blocks NF-κB signaling and suppresses the transcription of several pro-inflammatory cytokines through inhibition of the IκB kinase subunit IKKβ (IKK2). Studies show that TPCA-1 specifically inhibits IKKβ (IC₅₀ of 17.9 nM) and reduces inflammation and antigen-induced T cell proliferation in murine collagen-induced arthritis (1). TPCA-1 prevents recruitment of the transcription factor STAT3 to upstream kinases through interaction with the SH2 domain of STAT3. This limits the ability of cytokines and tyrosine kinases to induce STAT3 activity, which inhibits the ability of STAT3 to regulate cell growth and apoptosis. Treatment of non-small cell lung cancer (NSCLC) cells with TPCA-1 represses cell proliferation, suggesting that TPCA-1 may be effective in treating some forms of cancer (2). Studies have examined the ability of TPCA-1 to mediate the inflammatory response through control of IKKβ and STAT3 signaling in animal models of arthritis (1), chronic periodontitis (3), and nasal epithelial inflammation (4).